Effects of 8-(N-N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) on skinned myocardial fibres of the rat: reversible inhibition of calcium release from the sarcoplasmic reticulum.

The effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-3), which is reported to inhibit the release of intracellularly stored Ca2+ in skeletal and smooth muscles, were examined in ventricular myocardia of the adult rat. In skinned papillary muscle fibres with functional sarcoplasmic reticulum (SR) preserved, application of 100 or 300 microM TMB-8 during the Ca2+ loading period had no significant effect on the peak tension of subsequent caffeine-induced contraction, but when applied during exposure to caffeine, concentration-dependent reduction of the peak tension was observed. At 1000 microM, TMB-8 reduced the peak tension of caffeine-induced contraction when applied either during Ca2+ loading or during exposure to caffeine. TMB-8 had no substantial influence on the Ca(2+)-tension of skinned fibres without functional SR. In isolated papillary muscle preparations, TMB-8 prolonged the action potential duration and decreased the maximum rate of rise of potential, leading to abolition of contraction at 100 microM. In conclusion, TMB-8 may be a useful pharmacological tool for inhibiting Ca2+ release from SR, but only in skinned myocardial preparations.